Innate (and Innate-like) Lymphoid Cells: Emerging Immune Subsets With Multiple Roles Along Transplant Life

Abstract

Transplant immunology is currently largely focused on conventional adaptive immunity, particularly T and B lymphocytes, which have long been considered as the only cells capable of allorecognition. In this vision, except for the initial phase of ischemia/reperfusion, during which the role of innate immune effectors is well established, the latter are largely considered as "passive" players, recruited secondarily to amplify graft destruction processes during rejection. Challenging this prevalent dogma, the recent progresses in basic immunology have unraveled the complexity of the innate immune system and identified different subsets of innate (and innate-like) lymphoid cells. As most of these cells are tissue-resident, they are overrepresented among passenger leukocytes. Beyond their role in ischemia/reperfusion, some of these subsets have been shown to be capable of allorecognition and/or of regulating alloreactive adaptive responses, suggesting that these emerging immune players are actively involved in most of the life phases of the grafts and their recipients. Drawing upon the inventory of the literature, this review synthesizes the current state of knowledge of the role of the different innate (and innate-like) lymphoid cell subsets during ischemia/reperfusion, allorecognition, and graft rejection. How these subsets also contribute to graft tolerance and the protection of chronically immunosuppressed patients against infectious and cancerous complications is also examined. (Transplantation 2021;105: e322-e336).

The Reparative Roles of IL-33

“…These cells can be expanded in vivo and in vitro by IL-33, indicating that an early release of IL-33 after IRI might also contribute to the subsequent tissue injury through its effect on iNKT cells, supporting the emerging influential role of innate (and innate-like) cells in transplantation. 94-96 These concepts were supported in rodent IRI models where an IL-33 or NKT deficiency led to less myeloid cell recruitment after transplantation and protected against IRI. 97 DAMPs released from necrotic and damaged renal tubular epithelial cells (RTECs) act on healthy RTECs as well as immune cells, and induce TLRs expression and activation of inflammatory signaling pathways.…”

The Value of Single-cell Technologies in Solid Organ Transplantation Studies

“…96 Besides NK cells, ILCs further comprise 4 other subsets: ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells. 92 In recent years, it has become clear that, in addition to NK cells, other ILCs might play an important role in the allograft response as well. 97 For example, the presence of proinflammatory ILC1s may have a negative implication for the transplantation outcome by producing IFN-γ and TNF-α.…”

“…88,90 These NK cells are a subset of innate lymphoid cells (ILCs), which are immune cells that lack antigen-specific receptors but otherwise resemble the phenotype of the different CD4 + T helper cell subsets. 91,92 Broadly, NK cells can be divided into 2 subpopulations; the vast majority of NK cells are CD56 dim and are considered to have a cytotoxic phenotype, whereas a minor CD56 bright population is considered to mediate immune responses via the secretion of proinflammatory cytokines such as IFN-γ. 93,94 NK cells have been studied using single-cell approaches, 94,95 but the number of single-cell studies on NK cells in the context of SOT remains limited.…”

Potential correlation of allograft infiltrating group 2 innate lymphoid cells with acute rejection after liver transplantation

“…Nevertheless, given the tissue-resident properties of ILC2s, the distribution of the ILC2s in the liver allograft may be more relevant in driving the immune balance toward either a pro-inflammatory state (rejection) or an anti-inflammatory condition (tolerance) ( 16 ). In addition, previous studies have described that ILC2s might participate in transplant immunology ( 17 , 18 ). A recently published study by Huang et al.…”